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The Expression And Significance Of DEC1, HIF1α And STAT3 In Gastric Cancer Cell And Tissues

Posted on:2010-03-19Degree:MasterType:Thesis
Country:ChinaCandidate:B B LiFull Text:PDF
GTID:2144360278973825Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
ObjectiveTo investigate the expression of differentiated embryo-chondrocyte expressed gene1(DEC1),the signal tranducer and activator of transcription3 (STAT3) and hypoxia-inducible factor1α(HIF1α) in gastric cancer cell lines, such as BGC823 and SGC7901.Then to explore the expression of this three gene in gastric cancer tissues and to analyze the relationship between DEC1 and clinicopathological variables,that between DEC1 and STAT3,as well as HIF1 a.So we can detect the significance of DEC1 in gastric cancer and the role among the three gene in signal pathway taking part in carcinogenisis and development of gastric cancer.Methods(1) RT-PCR was used to detect mRNA expression of DEC1,STAT3 and HIF1αin gastric cancer cell lines,BGC823 and SGC7901;(2) Flowcytometry and immunocytochemistry were used to examine the protein expression of this three gene;(3) Western Blot was used for semiquantitive analysis of DEC1,GES-1 as controlled;(4) Immunohistochemistry was used to detect the expression of DEC1,STAT3 and HIF1αin 59 gastric cancer tissues,and 19 normal tissues depart from the tumor as controlled;then the relationship between DEC1 and clinicopathological variables was analyzed.Spearman correlation analysis was used to analyze the relationship between DEC1 and STAT3, and that between DEC1 and HIF1α.Result We found the mRNA expression of DEC1,STAT3 and HIF1αthrough RT-PCR,and the protein level expression by flowcytometry and immunocytochemistry in gastric cancer cell lines.Western Blot semiquantitive analysis found that DEC1 expression in gastric cancer cell lines was higher than that in GES-1.And the positive expression rate of DEC1 was significantly higher in gastric cancer tissues than that in benign lesion tissues.DEC1 expression was correlated with tumor grade(p<0.05),but not with patients'age, sex,tumor size,TNM staging,invasion depth,lymph node involvement and distant metastases(p>0.05).In normal tissues,DEC1 expression mostly lies in cytoplasm,but in gastric cancer tissues nuclear staining was stronger with tumor grade from well to poorly differentiated,especially in gastric signet-ring cancer. STAT3 was expressed in gastric cancer tissues,especially in poorly differeiated gastric cancer tissues and gastric signet-ring cancer tissues in which nuclear staining was evident.HIF1αwas also expressed in gastric cancer tissues, higher than that in benigh lesion tissues.Spearman correlation analysis showed that the expression of DEC1 in gastric cancer was related to STAT3 protein level,as well as HIF1αexpression.Conclusion(1) Our research confirmed that the expression of DEC1 in gastric cancer tissues and gastric cancer cell lines was significantly higher than that in normal tissued and gastric epithelial cells firstly.And the expression of DEC1 was stronger with tumor grade from well to poorly differentiated in gastric cancer tissues.It implied that DEC1 played an important role in the carcinogenesis and development of gastric cancer.(2) The result of Immunohistochemistry firstly showed the close relationship between DEC1 and HIF1αin gastric cancer tissues.Molecular mechanism may be that HIF1αinduced DEC1 expression by binding to HRE of DEC1 promoter,then target genes of down stream upregulated which maybe result in gastric carcinogenesis,providing a new mind for carcinogenesis.(3) The significant correlation between DEC1 and STAT3 which participated in carcinogenesis,was found in gastric cancer tissues firstly.The two genes belong to transcription factor,expressed higher in tumor.Our study implicated that the activation of the two genes inadequately may be one of the most important factors in gastric carcinogenesis and development.
Keywords/Search Tags:gastric cancer, DEC1, STAT3, HIF1α, cell differentiation
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